Many pathological conditions affecting humans and other animals are caused by infection with an RNA virus. Such viruses may be positive sense viruses (in which the viral genome has the same polarity as viral mRNA and may be directly translated), negative sense viruses (in which the viral genome is the complement of viral mRNA, and must be transcribed prior to translation) or double-stranded RNA viruses. Positive sense viruses include flaviviruses (e.g., hepatitis C virus); togaviruses (e.g., rubella virus, Sindbis virus, eastern and western encephalitis viruses) and picornaviruses (e.g., the enterovirus, polio virus, coxsackievirus, echovirus and rhinovirus).
In order to accurately diagnose and treat conditions caused by positive sense RNA virus infection, assays that are capable of sensitive detection of such viruses are needed. Most such assays focus on detecting the presence of viral nucleic acid and/or antigens. Such systems have the disadvantage that they cannot distinguish between active virus (capable of replication) and inactive virus, and they often lack the sensitivity that is necessary for a clinically reliable assay.
More recently, detection methods that take advantage of unique pathways of viral gene expression have been proposed. Such methods rely on the use of transgenic cell lines in which a virus-specific event triggers the production of a reporter protein. See Olivo, Clinical Microbiology Reviews 9:321-334, 1996; Park et al., Proc. Natl. Acad. Sci. USA 88:5537-5543, 1991; U.S. Pat. Nos. 5,591,579 and 5,418,132. However, it is unclear whether such systems can detect positive sense RNA viruses with the necessary sensitivity.
Accordingly, there is a need in the art for a system that permits the sensitive detection of active positive sense RNA viruses. The present invention fulfills this need and further provides other related advantages.